The ultimate goals of my career are to develop techniques to image tumor metabolism and to translate the knowledge gained from such imaging into improvements in cancer treatment. To this end I have focused on developing radiotracers that can be used with positron emission tomography (PET) to image cell proliferation. I have moved studies, which initially began in my laboratory using tissue culture and mice, to imaging patient's tumors and their response to treatment. This proposal will allow me to concentrate on the next important step in my career, the incorporation and testing of these techniques into the routine development of new chemotherapeutics agents and regimens. My goal is to help speed the development of new treatment modalities, by more rapidly determining if a regimen looks promising by imaging the accompanying metabolic changes. Ultimately, it is hoped that this will lead to a new paradigm for the evaluation of new cancer therapies. As the first step in the pathway, I will continue to work on the development of tracers to image the DNA synthetic pathway with PET. To make valid measurements of cellular proliferation using PET, I have developed the labeled pyrimidine analog [F-18]FLT, which is resistant to degradation and retained in cells by the action of thymidine kinase. Our pilot studies in dogs and humans indicate that this compound is retained in proliferating tissues and tumors and produces high contrast images. We propose to conduct a series of trials to determine the ability of FLT to detect different tumors and their response to therapy. We plan to incorporate this and similar agents into phase I and II clinical trials. This work is being conducted at the Barbara Ann Karmanos Cancer Institute/Wayne State University, a Comprehensive Cancer Center, which has an extensive record of work on new drug discovery and clinical drug testing. This includes the presence of a PO1 grant for the discovery of new agents and a UO1 grant for phase I testing of new drugs. There are also numerous investigator initiated protocols for the phase II testing of new drugs and their combinations, including some that I have initiated. We have already begun to include PET imaging as part of the evaluation of these protocols. This environment is also excellent for the development and mentoring of new faculty. I have been involved in the recruiting and fostering of new faculty through my roles as leader of a program within the Cancer Center and a section in the Division of Hematology/Oncology. This mentoring role is now being formalized as part of an ongoing plan within the Department of Internal Medicine to provide for regular reviews of and assistance to new faculty.